< Trở về

Research: Pfizer & Moderna: How mRNA companies disrupting the pharma industry?

Topic: 

Corporates

Event Summary

About three months after the first reported case of COVID19, Moderna developed a vaccine and began the clinical trial on humans on 16 March 2020, while Pfizer-BioNTech was 2 months behind (5 May 2020). However, in a surprising turn of event, Pfizer-BioNTech’s vaccine became the first in the world to receive authorisation for emergency use against COVID19, and Moderna followed behind. So, will Pfizer maintain its dominance following their lead in the COVID19 vaccine distribution... Or will they be overtaken by Moderna, the up and rising new horse? The global fight for vaccine distribution… Who do you think will win?

I. COMPANY OVERVIEW


1. PFIZER INC.

Pfizer Inc (NYSE:PFE) is a global research-based biopharmaceutical company that was listed on the stock exchange in June 1942. In actual fact, it has been around for more than 170 years! Initially known as Charles Pfizer and Company, it was started in 1894 by German cousins, Charles Pfizer and Charles Erhart in Brooklyn, New York. Over the years, it has progressed, and today, Pfizer is one of the top three giants in the pharmaceutical industry worldwide (Pfizer, 2021).

As of November 2020, Pfizer has 78,500 employees, over 200 suppliers, and owns 43 manufacturing sites globally. Every year, Pfizer produces more than 23 billion doses of medications for over 125 countries (Pfizer’s Scaling Up, 2020). In 2020, despite being affected by COVID 19, it generated $41.9 billion in revenue, a 1.8% growth from the previous year. (Pfizer Annual Report, 2020).

With that said, how can they not be on the vaccine developer list? In April 2020, Pfizer got into an agreement with BioNTech, a German biotechnology company specialized in cancer medicine, to develop, manufacture, and commercialize the mRNA-based coronavirus vaccine, BNT162.


2. MODERNA INC.


Conversely, Moderna Inc (NASDAQ GS:MRNA), formerly known as Moderna Therapeutics Inc, is an American biotechnology company based in Cambridge, Massachusetts. It was founded in 2010 and was listed on the stock exchange in Dec 2018. The company specializes in the use of messenger RNA (mRNA) to develop therapeutics and vaccines in areas of immuno-oncology, infectious diseases, rare diseases, cardiovascular diseases, and autoimmune diseases (Moderna’s Annual Report, 2020).


In January 2020, Moderna started developing a vaccine (mRNA-1273) for the novel coronavirus, which became the first commercialised product from the company in ten years. Previously, all its revenues were mainly from grants to aid in its R&D. As of March 2021, Moderna has over 1,500 employees, 8 partners in varying fields, and 24 development programs, of which 14 were in the clinical studies stage (Moderna, 2021).


II. HOW DID PFIZER & MODERNA BECOME THE FORERUNNERS IN THE VACCINE DISTRIBUTION?


For a vaccine to be marketed to the public, it has to go through 5 key stages. The first stage is the discovery & research stage where scientists and researchers conduct laboratory examinations on the virus and this usually takes 2 to 5 years. Second, is the preclinical stage where the vaccine is tested in animals and takes about 2 years. Third, the clinical development stage consists of Phase I, taking 1 to 2 years, Phase II taking 2 to 3 years, and Phase III taking 2 to 4 years. Testing is conducted in humans in the clinical development stage in gradually increasing sample sizes across the Phases. Four, is the regulatory review and approval stage which takes 1 to 2 years. Lastly, the manufacturing and delivery stage takes a varying amount of time depending on each company’s capabilities.


As such, a vaccine typically takes about 5 years to reach the human testing stage, and potentially more than 10 years to be fully authorised (Broom, 2020). The fastest a vaccine has ever been developed was 4 years, which is the mumps vaccine in 1967. So how did Pfizer and Moderna manage to push out the vaccine for human trials in such a short span of time?


1. MRNA TECHNOLOGY

Firstly, both Pfizer and Moderna use the new groundbreaking mRNA technology in their vaccines. mRNA are single stranded RNA molecules that complement the DNA strands. Unlike the DNA which stays in the nucleus, mRNA moves freely around the nucleus and cytoplasm to make proteins (Brody, n.d.). For the vaccine, the mRNA approach introduces strands of mRNA that send instructions to the body’s cells to produce copies of recognizable harmless virus protein where the human body eventually develops immunity. Traditionally, most vaccines introduce a weakened or inactivated version of the virus into the human body instead. Also known as the viral vector vaccines. However, this traditional approach takes about four to six weeks to reach adequate biomass to begin manufacturing the vaccine. Whereas, the mRNA technology was able to be synthesized within minutes as it uses readily available materials (source).


2. EXPERTISE IN R&D AND OTHER RESOURCES


Secondly, its strong expertise in research and development (R&D) and resources has also played a part. Before COVID, both Pfizer and Moderna have spent years studying and researching on various viruses, some of which includes the Severe Acute Respiratory Syndrome (SARS) which surfaced in 2002, and the Middle East Respiratory Syndrome (MERS) in 2012. The novel coronavirus, SARS-CoV-2, is part of a larger family of coronaviruses which includes SARS and MERS. SARS, MERS, and COVID are diseases that infect animals, evolve and cause illnesses in people. Even though there are still no vaccines for SARS and MERS, the years of studies have aided in the development of the COVID19 vaccine. In addition, while the mRNA approach to vaccines is new, what many people overlook is that there has been over 15 years of extensive research conducted on mRNA technology and its uses before it became successfully applied on the vaccines.


Moderna has been focusing on mRNA based technology to develop what is called a bioplatform since its incorporation. Bioplatforms are systems that have the ability to be easily scaled and redeployed for different diseases (source). Their expertise in this technology helped to speed up the process for the vaccine development significantly and gave them the competitive advantage.

Conversely, Pfizer being one of the top three giants in the pharmaceutical industry worldwide, there is no doubt about their capability. However, they do lack the expertise in mRNA technology. As such, a strategic collaboration was what brought them back to the playing field in vaccine development.


3. STRATEGIC COLLABORATION


Pfizer entered a strategic collaboration with BioNTech in early 2018 with a goal to jointly develop an mRNA-based influenza vaccine, which has then turned to the COVID19 vaccine (source). Pfizer contributed its broad expertise in R&D, regulatory capabilities and global manufacturing and distribution network while BioNTech aided in providing the clinical supply of the vaccine and its mRNA manufacturing facilities. The understanding and partnership established over the years gave them a huge advantage in this vaccine development (source).


Similarly, Moderna is not lacking behind. Shortly after Moderna announced plans to begin developing the vaccine, they clinched funding from the Coalition Epidemic Preparedness Innovations (CEPI) to accelerate the development process. Furthermore, Moderna also established a collaboration with the Vaccine Research Centre (VRC) of the National Institute of Allergy and Infectious Disease (NIAID), part of the National Institutes of Health to design the vaccine (source). These strategic collaborations provided Moderna with funding and access to extensive resources in R&D which they lacked internally.


4. FACTOR OF LUCK


More often than not, the factor of luck perhaps was also an influence. On average, the rate of failure in vaccine development is as high as 93%. At the start, there may be over 100 potential vaccines. However, as it passes through the stages, many get eliminated. For example, up to 100 potential vaccines may emerge at the discovery and research stage, but only about 20 move on to the preclinical stage, 10 move to Phase 1, 5 move to Phase 2, and ultimately maybe only 1 may reach the Phase 3 and approval stage (source). In this case, Pfizer and Moderna seem to be the lucky few.


IV. HOW ARE PFIZER’S & MODERNA’S VACCINE IN TERMS OF EFFICACY AND SAFETY?


Although the vaccines were developed in a short span of time, worries revolve around their efficacy against the SARS-Cov-2 virus and side effects. On a global stage, the World Health Organisation (WHO) has listed 8 vaccines on its Emergency Use List (EUL). These are Pfizer-BioNTech, AstraZeneca-SK Bio, Serum Institute of India, AstraZeneca EU, Janssen, Moderna, Sinopharm, and Sinovac (source). AstraZeneca-SKBio, Serum Institute of India, and  AstraZeneca EU are all versions of the AstraZeneca-Oxford COVID 19 vaccine, with the exception of different manufacturing sites, in Korea, India, and Sweden respectively.


1.  VACCINE EFFICACY

While there were some minor differences in the vaccines between Pfizer’s and Moderna’s, their efficacy against virus infection reached 94 to 95%, the highest among all other vaccines in the market. Based on WHO’s records, Pfizer-BioNTech is 95%, Astrazeneca-Oxford is 63.09%, Janssen (developed by Johnson & Johnson) is 66.3% , Moderna is 94.1%, Sinopharm is 79%, and Sinovac is 51% effective against the original strain of SARS-Cov-2 virus.


However, as the virus mutates over time, and more variants of concern begin surfacing, the question pops up once again. Will the vaccine be effective against these variants?

Currently, the variants of concern are the Alpha (B.1.1.7) variant, Beta (B.1.351) variant, Gamma (P.1) variant, and the Delta (B.1.617.2) variant which surfaced in the UK, South Africa, Brazil and India respectively. The delta variant is the most transmissible variant, contributing largely to the cases in the U.S., and driving up the number of cases globally.


Moderna’s studies, which did not include statistical figures, revealed that their vaccine is still highly effective against the delta variant but modestly less effective against the new variants as compared to the original strain of the coronavirus. Whereas Pfizer’s vaccine was said to be 88% effective in preventing infection against the delta variant from the UK real-world studies which happened in May. However, one month later, it dropped to 79% (source). The latest study conducted by Israel’s health ministry reported in July, mentioned that Pfizer’s vaccine is 93% effective against serious illness and hospitalisation, but only 64% effective against symptomatic situations (source).


Another collated research reported by Forbes which was published in June 2021 shows a comparison between Astrazeneca, Johnson, Pfizer and Moderna’s vaccine against the Original Strain, Alpha, Beta and Delta variant as shown in the illustration (source). While the figures may have differed, it is safe to say that the vaccines generally have a lower efficacy against the variants compared to the original strain. But, as most efficacy rates are above 50%, it is still better to be vaccinated than leaving it to chances.


2. SAFETY FACTOR: SIDE EFFECTS


Vaccination brings along mild-to-moderate side effects, which are normal. Common side effects include injection site pain, headache, muscle pain, fever, injection site swelling, among others. Side effects are signs that our immune system is working to attack the foreign molecule from the vaccine that is entering our body. However, does that mean not having side effects is a bad thing? That’s not necessarily the case! Scientists discovered that older people above 65 years old seem to experience lesser side effects and this could be due to lower antibody levels (source). Ultimately, the immune system works differently for each individual and many biological factors such as gender affects it. Not experiencing any side effects does not mean that the vaccine is not effective as cases revealed immunity is still present.


As a matter of fact, such side effects seem more prominent in individuals taking the Moderna vaccine. For Pfizer’s vaccine, adolescents below the age of 16 are more likely to experience it as compared to those above 16. In addition, outside of clinical trials, it has been reported that there are cases of severe allergic reactions, myocarditis (inflammation of heart muscle), and pericarditis (inflammation of outer lining of the heart) in both Pfizer and Moderna vaccines. However, Pfizer also reported cases of diarrhea, vomiting, pain in extremity, and other more serious adverse reactions.

Logically thinking, it seems that the mRNA vaccine would have less severe side effects as compared to the viral vectors since the substance is less harmful is that right? Currently, it seems to be the case. Astrazeneca vaccines which use the viral vector approach have reported rare cases of blood clotting syndrome, one of which was fatal in Australia (source). Nonetheless, it is important to note that such side effects are just a note to caution and cannot be compared against different vaccines. There are too many variables such as candidates in question and the number of people administering the vaccine, to make a representative comparison.


3. SAFETY FACTOR: STORAGE REQUIREMENTS


Another factor, which is of greater concern to the government, is the storage requirements. RNA vaccines are fragile and would require ultra-cold chain storage. This becomes an issue when transporting globally across different terrains and storing it till usage.


Pfizer’s vaccines have to be stored at an ultra-low temperature between -80ºC to -60ºC (-112ºF to -76ºF), away from sunlight and ultraviolet light in order to preserve it to the expiry date. (Pfizer-BioNTech Vaccine PDF). Even though they have invented a cutting edge packaging to maintain its temperature requirement up to 10 days during international shipping, it remains a challenge for many low- and middle-income economies when it comes to storage. Average pharmacies and clinics do not have the necessary facilities to store the vaccines.


Contrary to Pfizer’s vaccines, Moderna’s vaccines win against Pfizer’s in the temperature requirement. Moderna’s vaccines can be kept between -50ºC to -15ºC (-58ºF to 5ºF), away from direct light. (Source: Moderna Vaccine PDF & source). The temperature storage for Moderna’s vaccine can be achieved using standard freezers, thereby making storage more accessible and convenient as compared to Pfizer.


V. ARE THESE mRNA COMPANIES MAKING PROFITS?

Ultimately, this leads down to the figures… Are the companies making profits out of the vaccine? Unlike other vaccine developers such as Astrazeneca-Oxford who is supplying its vaccine at a not-for-profit price, Pfizer-BioNTech and Moderna are making profit out of it.


1. COMPONENTS IN R&D INVESTMENTS

Since both Pfizer/BioNTech and Moderna did not explicitly disclose their R&D investments, parts of those costs can be explained via public funding, and the signed agreements before vaccine approval (APAs).


Pfizer and BioNTech agreed on equally sharing both the R&D expenditures and profits made from their joint program. In total, they have $800M funds from the public funding supported by Germany and the EU Commission (source). Notably, Pfizer and BioNTech’s responses towards governmental funding were contradictory. While the former refused handouts from the Trump administration as they did not want any bureaucratic constraints, the latter has been granted $445M from German government to scale-up manufacturing capacity, as well as to accelerate clinical development in its home market (source). Other than that, they have raised $17,749M via APAs, with the EU (63%) being the largest investor and the U.S. (33.6%) being the second largest (source).


On the other hand, Moderna was largely dependent on grants from the U.S. in which it was funded $955M directly by the States, not to mention the APA worth $4.5B. To sum up, Moderna received $956M from direct funding and funding to intermediaries, and $7380 worth in APAs with the U.S. (61%) and the EU Commission (39%) (source).


2. VACCINE DISTRIBUTION AND ESTIMATED PROFIT MARGIN

Funding contribution to R&D investments might influence the priority of vaccine distribution which was clearly shown via records on profit distribution. In the first quarter of 2021, Pfizer/BioNTech reported around $5.9B in cumulated revenues solely from the Covid-19 vaccine sales in which 58% of sales were from the U.S. (Pfizer Q1 2021 PDF). Meanwhile, Moderna recorded $1.7B in revenue in the first quarter of 2021 in which the contribution of sales from the U.S. was a large 78% (Moderna Q1 2021 PDF).


The partnership’s higher revenue can be attributed to their larger scale manufacturing capability. In total, they project to manufacture 2.5 billion doses by the end of 2021, while Moderna expects to supply between 800 million and 1 billion doses. So far, Moderna has recognized 102 million doses as revenue in the first quarter (source) while Pfizer/BioNTech has already shipped 430 million doses as of May, 2021 (source).


Though Pfizer/BioNTech recorded a much larger cumulated revenue than Moderna, the latter performed better in terms of gross profit margin based on our estimation.


CONCLUSION

In terms of profit-making, Moderna seems to take the lead though Pfizer was able to distribute more doses and hence recognised higher revenue. Ultimately, the aim of a business is to maximise shareholder value, this in turn maximises profit and reduces cost in the long term. While the idea of making money out of the vaccine in this dire situation may seem unethical to some, the profit is necessary to sustain the business in the long run. In this global fight for vaccine distribution, Pfizer is likely to take the lead especially in comparison to Moderna. The expertise and foundation it has built up over the years has allowed it to make a vaccine that is of higher efficacy as compared to its peers. In addition, its brand and network of good relationships it has established over the years worldwide has helped in gaining the confidence of the public and clinching the agreements with various governments to drive vaccine distribution and eventually higher profitability.


REFERENCES

BBC News. (2020, December 8). Coronavirus: first Pfizer vaccine given to 90 year-old woman. BBC News. Retrieved from https://www.bbc.com/news/av/health-55153325

Broom, D. (2020, June 2). 5 charts that tell the story of vaccines today. World Economic Forum. Retrieved from https://www.weforum.org/agenda/2020/06/vaccine-development-barriers-coronavirus/

Brody, L, C. (n.d.). Messenger RNA (mRNA). National Human Genome Research Institute (NIH). Retrieved from https://www.genome.gov/genetics-glossary/messenger-rna

Moderna. (2021). About Us. Moderna. Retrieved from https://www.modernatx.com/about-us/moderna-facts

Pfizer. (2021). Pfizer Website. Retrieved from https://www.pfizer.com/

Pfizer Scaling Up. (2020, November). Breakthrough vaccine to potentially protect against the spread of COVID 19 [PDF file]. Pfizer.

Pfizer Annual Report. (2020). Pfizer Inc 2020 Annual Report [PDF file]. Pfizer.